Compositions and methods for treating corneal haze

Abstract

Disclosed herein are compositions and methods for treating corneal haze. Compositions and methods of use comprise therapeutically effective amounts of compounds that agonize the EP2 and/or EP4 receptor. Administration of the disclosed compounds can prevent and treat corneal haze development.

What is claimed: 
     
         1 . A method of treating corneal haze in an eye, by administering a composition comprising a therapeutically effective amount of a compound selected from the group consisting of an EP2 agonist, and EP4 agonist, and a combination thereof, whereby the corneal haze is treated. 
     
     
         2 . The method of  claim 1 , wherein the corneal haze is caused by photorefractive keratectomy (PRK), laser-assisted in-situ keratomileusis (LASIK), or laser epithelial keratomileusis (LASEK). 
     
     
         3 . The method of  claim 1 , wherein the compound is an EP2 agonist. 
     
     
         4 . The method of  claim 1 , wherein the compound is an EP4 agonist. 
     
     
         5 . The method of  claim 1 , wherein the compound is administered locally by eye drop, ointment, cream, or intraocular implant. 
     
     
         6 . A method of treating a corneal haze in an eye, by administering a composition comprising a therapeutically effective amount of a compound having a structure: 
       
         
           
           
               
               
           
         
         wherein each dashed line represents the presence or absence of a double bond; 
         R 1 , R 2  and R 3  are each independently selected from H or C 1 -C 6  linear alkyl; 
         R 4  is H, C 1 -C 6  alkyl, C 1 -C 6  alkenyl, a salt thereof, or an amine thereof; 
         X and Y are each independently selected from H, OH, ═O, Cl, Br, I, or CF 3 ; 
         Z 1  and Z 2  are each independently selected from CH or N; 
         W 1  and W 2  are each independently selected from CH, CH 2 , aryl or substituted aryl, heteroaryl, substituted heteroaryl; 
         m is 0 to 4; 
         p is 0 or 1; 
         o is 0 to 4; and 
         V is CH 3 , aryl, aryl or substituted aryl, heteroaryl, substituted heteroaryl. 
         wherein the administration treats the corneal haze. 
       
     
     
         7 . The method of  claim 6 , wherein V is 
       
         
           
           
               
               
           
         
         wherein R 5  is halogen, C 1 -C 6  alkyl, or C 1 -C 6  alkenyl; 
         n is 0-7; and 
         U is S or O. 
       
     
     
         8 . The method of  claim 6 , wherein n is 1, U is S and R 5  is Cl. 
     
     
         9 . The method of  claim 6 , wherein W 2  is thiophene. 
     
     
         10 . The method of  claim 6 , wherein the compound has the structure: 
       
         
           
           
               
               
           
         
       
     
     
         11 . The method of  claim 6 , wherein the compound has the structure: 
       
         
           
           
               
               
           
         
       
     
     
         12 . The method of  claim 6 , wherein the compound has the structure: 
       
         
           
           
               
               
           
         
       
     
     
         13 . The method of  claim 6 , wherein the compound has the structure: 
       
         
           
           
               
               
           
         
       
     
     
         14 . The method of  claim 6 , wherein the compound has the structure: 
       
         
           
           
               
               
           
         
       
     
     
         15 . A method of maintaining transparency of a cornea by administering a composition to said cornea, wherein said composition comprises a compound selected from the group consisting of an EP2 agonist, EP4 agonist, and a combination thereof. 
     
     
         16 . The method of  claim 15 , wherein the composition is administered prior to, during or after a procedure selected from PRK, LASEK, or LASIK. 
     
     
         17 . The method of  claim 15 , wherein the compound has a structure: 
       
         
           
           
               
               
           
         
       
     
     
         18 . The method of  claim 15 , wherein the compound has a structure: 
       
         
           
           
               
               
           
         
       
     
     
         19 . The method of  claim 15 , wherein the compound has a structure: 
       
         
           
           
               
               
           
         
       
     
     
         20 . The method of  claim 15 , wherein the compound has a structure: 
       
         
           
           
               
               
           
         
       
     
     
         21 . The method of  claim 15 , wherein the compound has a structure: 
       
         
           
           
               
               
           
         
       
     
     
         22 . A method of inhibiting transformation of a fibroblast to a myofibroblast in an eye, by administering a composition comprising a therapeutically effective amount of an EP2 agonist, an EP4 agonist or a combination thereof, wherein the administration inhibits transformation of a fibroblast to a myofibroblast. 
     
     
         23 . The method of  claim 22 , wherein by inhibiting transformation of the fibroblast to the myofibroblast, corneal haze is prevented or reduced. 
     
     
         23 . The method of  claim 22 , wherein by inhibiting transformation of the fibroblast to the myofibroblast corneal transparency is maintained. 
     
     
         24 . The method of  claim 22 , wherein the composition is administered prior to, during, or after a corrective procedure. 
     
     
         25 . The method of  claim 24 , wherein the corrective procedure is PRK, LASIK, or LASEK.